5 ms·

> You can't gauge the specific danger or benefit of the unknown. I’m not claiming to. All I’m saying is that “CRISPR [isn’t] dangerous specifically because we

by klmr 8y ago

> You can't gauge the specific danger or benefit of the unknown. I’m not claiming to. All I’m saying is that “CRISPR [isn’t] dangerous specifically because we underestimate the complexity of DNA”. In the context of this discussion I can go much further, though: the physiological presence of i-motifs doesn’t change the hazard or risk of CRISPR whatsoever. We know this because our risk assessment of CRISPR never relied on the non-existence of i-motifs.

subroutine 8y ago
Is this necessarily true though? Do you think the situation I illustrate here is not possible (crappy photoshop of cas9 guide RNA matching a DNA sequence across a 'imotif'): https://i.imgur.com/huIKqyD.png https://i.imgur.com/huIKqyD.png
- ethbro 8y ago
  Parent and microbiologists can correct me if I'm wrong, but the primary drivers of current DNA tampering are correlating different forms of genes with health outcomes. We aren't creating new genetic code ex nihilo (yet). So understanding the nuances of how different forms of genes influence outcomes is less important than knowing that they do. And what the naturally-occurring "correct" form looks like.
  - subroutine 8y ago
    One of the main drivers of CRISPR-Cas9 biotech development is to perform targeted single-nucleotide DNA editing, to cure or significantly reduce the risk of getting a disease. Numerous diseases have a genetic component; some people have a higher risk of getting a disease due to their genetic makeup. Often a significant amount of the risk is attributed to a 'single nucleotide polymorphism' or 'SNP' (this is known to be true for diseases like sickle-cell anemia, cystic fibrosis, Alzheimer's disease, and others). If we could alter this SNP however, from the disease-associated nucleotide to the control nucleotide, theoretically this would substantially reduce the risk of getting that disease. CRISPR-Cas9 allows us to do that. This process relies on fabricating an RNA-guide sequence to match the segment of DNA we want edited; and if we are careful, we make sure this Guide RNA matches ONLY this segment of DNA and nowhere else in the genome. If the Guide RNA matches some other random segment of DNA, it will result in 'off-target' edits. Now, this shouldn't really be an issue if we perform whole-genome sequencing on an individual prior to making the Guide RNA. We can just make sure the Guide RNA doesn't match anywhere else in their genome and all is well, right?! Well... maybe not. Maybe these i-Motifs will fuck us over like in the picture I linked above.
- klmr 8y ago
  No, I think it’s totally possible (albeit exceedingly unlikely). But we already know that CRISPR has (rare) off-target effects. That’s why I’m saying that the i-motifs don’t change the risk assessment. At best, they can explain why CRISPR sometimes misbehaves (although it’s much more likely due to just plain old nonspecific binding in most cases).

by klmr 8y ago

subroutine 8y ago

Is this necessarily true though? Do you think the situation I illustrate here is not possible (crappy photoshop of cas9 guide RNA matching a DNA sequence across a 'imotif'): https://i.imgur.com/huIKqyD.png https://i.imgur.com/huIKqyD.png

ethbro 8y ago
Parent and microbiologists can correct me if I'm wrong, but the primary drivers of current DNA tampering are correlating different forms of genes with health outcomes. We aren't creating new genetic code ex nihilo (yet). So understanding the nuances of how different forms of genes influence outcomes is less important than knowing that they do. And what the naturally-occurring "correct" form looks like.
- subroutine 8y ago
  One of the main drivers of CRISPR-Cas9 biotech development is to perform targeted single-nucleotide DNA editing, to cure or significantly reduce the risk of getting a disease. Numerous diseases have a genetic component; some people have a higher risk of getting a disease due to their genetic makeup. Often a significant amount of the risk is attributed to a 'single nucleotide polymorphism' or 'SNP' (this is known to be true for diseases like sickle-cell anemia, cystic fibrosis, Alzheimer's disease, and others). If we could alter this SNP however, from the disease-associated nucleotide to the control nucleotide, theoretically this would substantially reduce the risk of getting that disease. CRISPR-Cas9 allows us to do that. This process relies on fabricating an RNA-guide sequence to match the segment of DNA we want edited; and if we are careful, we make sure this Guide RNA matches ONLY this segment of DNA and nowhere else in the genome. If the Guide RNA matches some other random segment of DNA, it will result in 'off-target' edits. Now, this shouldn't really be an issue if we perform whole-genome sequencing on an individual prior to making the Guide RNA. We can just make sure the Guide RNA doesn't match anywhere else in their genome and all is well, right?! Well... maybe not. Maybe these i-Motifs will fuck us over like in the picture I linked above.
klmr 8y ago
No, I think it’s totally possible (albeit exceedingly unlikely). But we already know that CRISPR has (rare) off-target effects. That’s why I’m saying that the i-motifs don’t change the risk assessment. At best, they can explain why CRISPR sometimes misbehaves (although it’s much more likely due to just plain old nonspecific binding in most cases).